RESUMEN
Mice deficient in the extracellular matrix protein tenascin-R (TN-R-/- mice) show several indices of impaired perisomatic inhibition in hippocampal slices. The present study examined electroencephalograms (EEGs) and auditory-evoked potentials (AEPs) in freely moving TN-R-/- and wild-type control mice, focusing on the hippocampal CA1 field and cerebral cortex. TN-R-/- mice expressed normal high-frequency oscillations (ripples) in CA1 and only a slight reduction of peak theta frequency. In contrast, their hippocampal gamma oscillations were significantly enhanced in amplitude. Also, the amplitude of the cortical EEG of TN-R-/- mice was increased over a wide frequency range. The amplitude of cortical and, to a lesser degree hippocampal, AEPs was clearly enhanced in TN-R-/- mice. In addition, response habituation to repeated sound stimuli was significantly attenuated in TN-R-/- mice. These findings indicate that tenascin-R is involved in the regulation of certain inhibitory mechanisms in the intact brain.
Asunto(s)
Corteza Cerebral/metabolismo , Potenciales Evocados Auditivos/fisiología , Hipocampo/metabolismo , Neuronas/metabolismo , Tenascina/deficiencia , Estimulación Acústica/métodos , Animales , Electroencefalografía/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Tenascina/genéticaRESUMEN
Histaminergic activity shows a clear circadian rhythm: high levels during the active period (in rodents at night, in monkeys and humans during the day), and low levels during the sleep period. Histamine appears to be necessary for the maintenance of the circadian rhythmicity of the adrenocortical hormone release, locomotor activity and food intake, and the sleep-wakefulness cycle. In addition, a role for histaminergic neurons in the light entrainment is implicated. In phase shift studies, histamine given centrally seems to entrain the activity rhythm in the same way as light impulses and inhibition of histamine synthesis seems to block the entrainment by light. Importantly, histamine participates in the control of arousal and may be implicated in the sleep disturbances in hepatic encephalopathy. Furthermore, evidence suggests a role for histamine in overall neuronal excitability and seizure susceptibility both in animals and humans. Thus, we conclude that histamine may exert modifying effects on circadian rhythmicity and neuronal excitability.
Asunto(s)
Nivel de Alerta/fisiología , Ritmo Circadiano/fisiología , Histamina/fisiología , Fases del Sueño/fisiología , Animales , Encefalopatía Hepática/fisiopatología , Humanos , Área Hipotalámica Lateral/fisiopatología , Red Nerviosa/fisiopatología , Neuronas/fisiología , Convulsiones/fisiopatología , Núcleo Supraquiasmático/fisiopatologíaRESUMEN
Neuropeptide Y (NPY) has been reported to profoundly influence and regulate brain circuits involved in a number of behaviours, like anxiety, alcohol intake, pain and energy homeostasis. Here we show that NPY increases sedation induced by different types of anaesthetics through interactions with the Y1 receptor. Consistently, in Y1-/- (homozygote knockout) mice NPY does not potentiate the pentobarbital-induced sedation. Similar results were obtained for avertin but not for ketalar- (NMDA antagonist) induced sedation. Local microinjection of NPY exhibited the strongest potentiating effect on pentobarbital-induced sedation in the posterior hypothalamic area and Y1 expression was found in the dorsal-premammillary and medial part of medial mammillary nuclei. These results show that Y1 is essential for NPY-induced enhancement of sedation and place this activity of NPY in the posterior hypothalamic area, a region of the brain previously implicated in the regulation of the wake-sleep cycle.
Asunto(s)
Interacciones Farmacológicas/fisiología , Hipotálamo Posterior/efectos de los fármacos , Neuronas/metabolismo , Neuropéptido Y/farmacología , Receptores de Neuropéptido Y/efectos de los fármacos , Sueño/efectos de los fármacos , Vigilia/efectos de los fármacos , Anestésicos/farmacología , Animales , Etanol/análogos & derivados , Etanol/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Moduladores del GABA/farmacología , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Hipnóticos y Sedantes/farmacología , Hipotálamo Posterior/citología , Hipotálamo Posterior/metabolismo , Ketamina/farmacología , Ratones , Ratones Noqueados , Neuronas/citología , Neuropéptido Y/metabolismo , Pentobarbital/farmacología , ARN Mensajero/metabolismo , Receptores de Neuropéptido Y/genética , Receptores de Neuropéptido Y/metabolismo , Sueño/fisiología , Vigilia/fisiología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The present study characterized the intensity-response functions of extracellular field responsiveness of different cortical/subcortical structures of the forebrain following the free-field presentation of tone stimuli, within a population of genetically audiogenic seizure (AGS)-prone KM-Wistar rats. The neural response properties of each case were compared to its propensity to exhibit AGSs during the continuous tone stimulation (15 kHz, 90 s at max.). The amplitudes or slope components of the evoked responses and their peak latencies showed significant positive (amplitude and slope) and negative (peak latency) Bolzmann's sigmoid relationships with the onset-latency of AGS. These relationships, with areal differences in the slopes of saturation functions, applied for the three different data sets recorded simultaneously from the stratum radiatum dendritic layer of the hippocampal CA1 area, primary auditory cortex layers II-IV, and frontal cortex surface. In addition, the similar type of functions between the evoked response variables and AGS onset latency held when all the areas were considered together. These data suggest that the neural responsiveness to acoustic stimulation of the primary sensory, multimodal and association cortices of the forebrain may altogether contribute to the seizure initiation by that modality in the genetically AGS-prone rats. It has been previously shown that there exist abundant and dispersed auditory projections from these forebrain areas to the brain stem and spinal cord, structures that are generally considered to be the key predisposing factors in the generation of AGS. Hence, the types of correlation found reflect the subject-specific stage of forebrain responsiveness, being either related or unrelated to genetic AGS-specific changes, and possibly its triggering impact upon the lower brain AGS network. Accordingly, the mere comparison of forebrain response measures of these AGS-prone animals with those of the AGS-resistant ones could not reveal the result presented.
Asunto(s)
Prosencéfalo/fisiología , Convulsiones/genética , Convulsiones/fisiopatología , Estimulación Acústica , Animales , Corteza Auditiva/citología , Corteza Auditiva/fisiología , Dendritas/fisiología , Electrofisiología , Potenciales Evocados Auditivos/fisiología , Hipocampo/citología , Hipocampo/fisiología , Prosencéfalo/citología , Ratas , Ratas WistarRESUMEN
To find out whether the changes in the brain histaminergic system are involved in the pathophysiology of portal-systemic encephalopathy, we examined the effects of histamine H(1) receptor blockade on spontaneous locomotor activity, feeding, and circadian rhythmicity in rats with portacaval anastomosis (PCA). Pyrilamine, an H(1) receptor blocker (15 mg/kg/day), was delivered with osmotic minipumps. Spontaneous locomotor activity was recorded for 72 hours in the open-field with an electromagnetic detector. Food intake was monitored twice daily at the end of the light (7 PM) and the dark (7 AM) phases for 3 days. Histamine H(1) receptor density in the suprachiasmatic nucleus (SCN) was examined with receptor autoradiography, employing [(3)H]pyrilamine. PCA surgery led to decreased movement time and velocity and flattened amplitude of the circadian rhythms of locomotion and feeding. In sham-operated rats, pyrilamine significantly decreased the movement time and velocity, as well as the total food consumption and completely abolished the circadian rhythmicity of locomotion. In contrast, pyrilamine increased the movement time and velocity in PCA-operated rats, particularly in the dark phase, and improved the precision of the circadian rhythms of locomotion and feeding. Histamine H(1) receptor density was not altered by PCA surgery, whereas pyrilamine treatment led to the complete blockade of H(1) receptors in both sham- and PCA-operated rats. We suggest that histaminergic imbalance has contributed to the generation and maintenance of the decreased spontaneous locomotor activity and altered circadian rhythmicity following PCA surgery in the rat, probably via an H(1) receptor-mediated mechanism.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1/farmacología , Actividad Motora/efectos de los fármacos , Derivación Portocava Quirúrgica , Pirilamina/farmacología , Animales , Atrofia , Autorradiografía , Ritmo Circadiano/efectos de los fármacos , Ritmo Circadiano/fisiología , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Ligandos , Hígado/patología , Masculino , Ratas , Ratas Wistar , Receptores Histamínicos H1/metabolismo , Núcleo Supraquiasmático/metabolismo , Factores de TiempoRESUMEN
The most common adaptive filtering method is based on the least mean square (LMS) algorithm, which updates the filter coefficients by a gradient based method. The convergence properties of the LMS algorithm can be improved by updating the filter coefficients in the frequency domain. This work presents a new LMS algorithm, which updates the filter coefficients in the cosine transform domain. Instead of a constant gain factor in the coefficient updating the present method uses a time-varying optimized gain factor. This yields a considerably improved convergence performance. The algorithm was applied to the EEG activity analysis of freely behaving rats.
Asunto(s)
Algoritmos , Electroencefalografía/métodos , Procesamiento de Señales Asistido por Computador , Animales , Artefactos , Conducta Animal/fisiología , Lóbulo Frontal/fisiología , Neocórtex/fisiología , Ratas , Ratas Endogámicas , Ratas Wistar , Factores de TiempoRESUMEN
To determine whether the increased histamine levels in the brain of rats with portacaval anastomosis (PCA) are associated with the development of sleep disturbances during the light phase, the neocortical slow-wave activity of PCA-operated rats was examined with electroencephalography (EEG) 1 month and 6 months after the surgery. The tissue levels of histamine, tele-methylhistamine, 5-hydroxytryptamine (5-HT) (serotonin), and 5-hydroxyindole-3-acetic acid (5-HIAA) in frontal cortex were assayed by high-performance liquid chromatography 6 months after the surgery. PCA surgery led to changes in the synchronized, low-frequency, high-amplitude frontal cortex EEG activity recorded during the light phase. Delta-wave amplitude but not delta time was significantly decreased, whereas both spindle amplitude and spindling time were significantly decreased. There were also significant age-related changes, presented as increases in the duration of spindles and the amplitude of both delta waves and spindles. PCA-operated rats showed a change in the pattern of EEG activity with increasing age similar to sham-operated rats. This suggests that once established, the resetting of the systems regulating the sleep-waking behavior is being maintained with time. The tissue levels of both histamine and metabolite in the frontal cortex were increased, whereas the serotonin system showed only an increase in the level of the metabolite. There was a significant negative correlation between the spindling time and the tissue histamine levels. We suggest that histamine, which participates in the control of vigilance, sleep, and wakefulness, as well as in the modulation of circadian rhythmicity, may play a role in the development of sleep disturbances in rats with PCA.
Asunto(s)
Encéfalo/metabolismo , Electroencefalografía , Lóbulo Frontal/fisiología , Histamina/metabolismo , Derivación Portocava Quirúrgica , Animales , Peso Corporal , Ácido Hidroxiindolacético/metabolismo , Hígado/anatomía & histología , Masculino , Metilhistaminas/metabolismo , Tamaño de los Órganos , Ratas , Ratas Wistar , Serotonina/metabolismo , Sueño/fisiologíaRESUMEN
The fasciculus retroflexus (FR) fiber bundle comprises the intense cholinergic projection from the medial division of the habenula nucleus (Hbn) of the epithalamus to the interpeduncular nucleus (IPN) of the limbic midbrain. Due to the widespread connections of the Hbn and IPN, it could be surmised that the FR is integrated in the processings of various subsystems that are known to be involved in the sleep-wake mechanisms; relevant sites include the limbic forebrain and midbrain areas and more caudal pontine structures. Consequently, the present study addressed the significance of the FR in the spontaneous sleep-wake stage-associated variations of the different activity patterns of frontal cortex and hippocampal electroencephalograms (EEGs), the electrooculogram, and body movements, in freely behaving rats that had been subjected to either bilateral electrolytic lesioning of the FR or control operations. The evolution of different state combinations was assessed by the combinatory analysis of different activity stages appearing on the 6-h records. As compared to the control-operated group, the FR lesioning substantially reduced the time spent in rapid eye movement (REM) sleep by 79%, moderately decreased the duration of the intermediate state of sleep by 29%, and quiet waking state by 44%, but had virtually no effects on the durations of different types of non-REM sleep (i.e., drowsiness that which involved quiet sleep or slow-wave sleep containing delta and spindle state components) or on the times of active waking behavior that corresponded to the body movements. Quantitative decomposition analyses revealed marked variations in the frontal cortex and hippocampal activity as well as REM during the course of the extracted sleep-wake stages described and there were also some group differences. Of those individual features that were used to determine different sleep-wake stages, the overall hippocampal theta time (41% decrease) and single REM frequency (71% reduction during the REM sleep) were most affected. In contrast, the various properties of desynchronization/synchronization patterns of frontal cortex EEGs were consistently hardly influenced by the FR lesioning. Therefore, the present data suggest the involvement of the FR in the REM sleep processes by establishing prominent associations with the limbic and REM control mechanisms that involve the hippocampus and plausibly pontine ocular activity networks.
Asunto(s)
Epitálamo/fisiología , Habénula/fisiología , Hipocampo/fisiología , Sistema Límbico/fisiología , Mesencéfalo/fisiología , Sueño REM/fisiología , Animales , Mapeo Encefálico , Electroencefalografía , Movimientos Oculares/fisiología , Masculino , Vías Nerviosas/fisiología , Ratas , Ratas Wistar , Fases del Sueño/fisiología , Ritmo Teta , Vigilia/fisiologíaRESUMEN
Histaminergic H3 receptor antagonists stimulate neuronal histamine release and could consequently have a number of physiological effects in the brain. The effects of H3 receptor blockade, induced by systemically administered thioperamide, were assessed on the frontal cortex electroencephalographic (EEG) properties in freely behaving rats. The relationship of EEG activity variables to endogenous brain histaminergic markers was also examined, both in controls and in portocaval anastomosis (PCA)-operated rats (which show increased levels of brain histamine and t-methylhistamine). Thioperamide reduced the incidence of thalamus-regulated EEG spindles, while it slightly increased their amplitude. It furthermore reduced the spectral power of low-frequency (1.5-5Hz) EEG, which effect was equally distributed over the spindle and non-spindle EEG states. These EEG effects were accompanied by increased motor activity of the animals. Both the low-frequency EEG activity and spindle incidence correlated inversely with the histamine level of the brain (hypothalamus and cerebellum excluded) while t-methylhistamine level correlated with the degree of thioperamide-induced reduction of slow-wave EEG activity. The present results provide evidence for the involvement of endogenous brain histamine level, histamine release (as assessed by t-methylhistamine level) and H3 receptors in the histaminergic regulation of neocortical synchronization patterns assumed to be linked to arousal control.
Asunto(s)
Corteza Cerebral/fisiología , Electroencefalografía , Histamina/fisiología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Histamina/metabolismo , Antagonistas de los Receptores Histamínicos/farmacología , Luz , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Tamaño de los Órganos , Piperidinas/farmacología , Derivación Portocava Quirúrgica , Ratas , Ratas WistarRESUMEN
The present study examines the effects of noradrenergic lesions (either DSP-4 i.p. or 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle on biochemical (noradrenaline (NA), dopamine (DA), serotonin (5-HT) and choline acetyltransferase (ChAT) activity) and cortical EEG (quantitative EEG (qEEG) and high-voltage spindle (HVS)) activity in young and aged rats. Near complete 6-OHDA NA lesions, but not partial DSP-4 NA lesions, increased HVS activity in young rats. DSP-4 and 6-OHDA lesions produced no significant changes in the 5-HT or DA levels or in the ChAT activity in young rats. In some of the aged rats, DSP-4 produced similar biochemical and HVS effects, as it induced in young rats. In the remainder of the aged rats, NA levels were greatly and 5-HT levels slightly decreased. DA levels and ChAT activity were unaltered in either set of aged rats. HVS activity was increased only in that group of aged rats with the greatly lowered NA content. These results suggest that: (1) some of the aged rats are more sensitive to DSP-4 treatment than young adult rats; and (2) NA depletions have to be complete to produce an increase in HVS activity in young and aged rats.
Asunto(s)
Envejecimiento/efectos de los fármacos , Bencilaminas/toxicidad , Química Encefálica/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Simpatomiméticos/toxicidad , Animales , Colina O-Acetiltransferasa/metabolismo , Dopamina/metabolismo , Masculino , Norepinefrina/metabolismo , Oxidopamina , Ratas , Ratas Endogámicas , Serotonina/metabolismoRESUMEN
Lesions causing loss of hippocampal theta activity have been shown to result in spatial memory deficits in rats. On the other hand, hippocampal theta activity is thought to be associated only with motor activity, and its role in learning/memory is not clear. Vigabatrin, an inhibitor of GABA-tranasminase, causes elevation of brain GABA levels. Previously, we have found that subchronic administration of vigabatrin did not impair spatial learning/memory in a water maze task. This experiment was carried out to further examine the hippocampal effects of vigabatrin by studying whether vigabatrin at antiepileptic doses affects mobility-related hippocampal EEG. Administration of vigabatrin (100 mg/kg or 500 mg/kg, IP) to nonepileptic rats caused no significant changes in mobility-related rhythmic theta activity, and the relative spectral power of theta frequency had a slight increasing tendency. These results suggest that the vigabatrin-induced enhanced GABAergic inhibition does not disturb normal mobility-related hippocampal theta activity.
Asunto(s)
Aminocaproatos/farmacología , Anticonvulsivantes/farmacología , Hipocampo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Ritmo Teta/efectos de los fármacos , Ácido gamma-Aminobutírico/metabolismo , Animales , Masculino , Ratas , Ratas Endogámicas , Valores de Referencia , VigabatrinRESUMEN
The present study investigates the effects of a serotonin (5-HT) reuptake inhibitor, alaproclate, on water maze cued navigation performance in serotonin depleted and control rats. Treatment with p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, (400 mg/kg/day x 3 i.p.) significantly depleted cerebral levels of both 5-HT (about 80% depletion) and its major metabolite 5-HIAA (about 90% depletion) for at least 7 days. PCPA treatment also slightly decreased cerebral noradrenaline and dopamine levels (16% and 22% reductions, respectively). PCPA treatment alone had no effect on the acquisition of the cued navigation version (visible platform) of the water maze task measured as the distance to find the escape platform, but it significantly increased swimming speeds of the rats. Alaproclate (20 mg/kg i.p.) increased escape distance and slightly decreased swimming speeds of the rats. The effects of alaproclate did not differ between PCPA and sham treated (arabic gum 400 mg/kg/day x 3 i.p.) rats. The results demonstrate that alaproclate induced cued navigation behavioral deficit is maintained after a marked depletion of cerebral serotonin.
Asunto(s)
Alanina/análogos & derivados , Antidepresivos/farmacología , Señales (Psicología) , Fenclonina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Alanina/farmacología , Animales , Monoaminas Biogénicas/metabolismo , Química Encefálica/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Serotonina/fisiología , NataciónRESUMEN
The present study investigates the effects of gammavinylgaba (GVG, 4 days treatment at 50 and 200 mg/kg), a gabatransaminase inhibitor, on the high-voltage spindle (HVS) activity in control and nucleus basalis-lesioned rats. GVG treatment at 200 mg/kg, but not at 50 mg/kg increased HVS activity in controls. GVG greatly aggravated nucleus basalis magnocellularis (NBM) lesion-induced increase in HVS activity at 200 mg/kg, but not at 50 mg/kg. The present results demonstrate that partial NBM lesions increase the HVS inducing potency of GVG.
Asunto(s)
4-Aminobutirato Transaminasa/antagonistas & inhibidores , Aminocaproatos/farmacología , Electroencefalografía/efectos de los fármacos , Sustancia Innominada/fisiología , Ácido gamma-Aminobutírico/fisiología , Animales , Masculino , Ratas , Ratas Wistar , Factores de Tiempo , VigabatrinRESUMEN
The present study investigated whether an overactive noradrenergic system is related to the impairment in learning/memory in aged subjects. The effects of partial noradrenaline depletion (using the noradrenergic neurotoxin DSP-4) on the acquisition of a water maze task was investigated in young and aged rats, and hippocampal noradrenaline content was correlated with spatial learning performance in similar rats. DSP-4 treatment impaired markedly the acquisition of the water maze task in aged rats, but improved it slightly in young rats. DSP-4 treatment decreased swimming speed, and this effect tended to be more marked in young rats. In the group of control rats, hippocampal noradrenaline tended to correlate positively with spatial bias in aged rats (the rats with the highest noradrenaline content in the hippocampus tended to have the best spatial learning/memory), but negatively in young rats. These results do not support the hypothesis that spatial learning/memory impairment is due to an overactive noradrenergic system in aged rats. Further studies are needed to clarify the reasons of the marked age-related difference in the effects of DSP-4 on the performance of water maze task in rats.
Asunto(s)
Bencilaminas/farmacología , Orientación/efectos de los fármacos , Percepción Espacial/efectos de los fármacos , Simpatomiméticos/farmacología , Envejecimiento/metabolismo , Envejecimiento/psicología , Animales , Química Encefálica/efectos de los fármacos , Cognición/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Aprendizaje/efectos de los fármacos , Masculino , Norepinefrina/metabolismo , Norepinefrina/fisiología , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
The present study examines whether tetrahydroaminoacridine (THA) can improve the deterioration in passive avoidance (PA) retention performance induced by medial septal (MS) and fimbria-fornix (FF) lesions in young rats or by aging. Retention of young MS-lesioned rats was improved by pretraining injection of THA at 3 mg/kg, but not by THA at 1 mg/kg or by either of the posttraining doses of THA (1 and 3 mg/kg). Pretraining injections of THA at 1 or 3 mg/kg had no effect on the PA retention performance of FF-lesioned rats. Age-induced PA failure was alleviated by pretraining administration of THA at 1 and 3 mg/kg. Posttraining injections of THA (1 or 3 mg/kg) had no effect on PA retention performance of aged rats. These results demonstrate that 1) THA may improve hippocampal cholinergic denervation-induced functional deficits and 2) some of the age-related PA deficits may be due to a cholinergic deficit and can be reversed with THA.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Hipocampo/fisiología , Memoria/efectos de los fármacos , Tacrina/farmacología , Envejecimiento , Animales , Colina O-Acetiltransferasa/análisis , Inhibidores de la Colinesterasa/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/fisiología , Especificidad de Órganos , Ratas , Ratas Endogámicas , Análisis de RegresiónRESUMEN
Quisqualic acid NBM lesions had no effect on water maze performance, but slightly impaired passive avoidance acquisition. GammavinylGABA treatment alone had no effect on the passive avoidance and water maze performance, but aggravated acquisition deficit in rats subjected to NBM lesioning. However, gammavinylGABA-treated NBM-lesioned rats reached control level of performance.
Asunto(s)
Conducta Animal/fisiología , Sustancia Innominada/fisiología , Transmisión Sináptica , Ácido gamma-Aminobutírico/fisiología , 4-Aminobutirato Transaminasa/antagonistas & inhibidores , Aminocaproatos/farmacología , Análisis de Varianza , Animales , Masculino , Actividad Motora/fisiología , Ácido Quiscuálico , Ratas , Ratas Endogámicas , Sustancia Innominada/efectos de los fármacos , Sustancia Innominada/patología , VigabatrinRESUMEN
In the present study the effect of combined anticholinesterase [tetrahydroaminoacridine (THA)] and alpha2-antagonist (antipamezole) treatment were evaluated on nucleus basalis (NB, quisqualic acid) lesion-induced EEG activity changes. THA (1, 3 and 6 mg/kg; an anticholinesterase) and atipamezole (Ati: 3 and 10 mg/kg; an alpha2-antagonist) suppressed dose-dependently NB lesion-induced high-voltage spindle activity and increase in slow/fast activity ratio. A combination of THA (3 mg/kg) and Ati (3 or 10 mg/kg) more effectively suppressed NB lesion-induced HVS activity than either of the drugs alone did. The present results suggest that alpha2-noradrenergic and NB cholinergic systems interact in the regulation of slow wave and HVS activity and that combined stimulation of these systems more effectively stabilize NB lesion-induced EEG changes.
Asunto(s)
Electroencefalografía , Imidazoles/farmacología , Sustancia Innominada/efectos de los fármacos , Tacrina/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Animales , Colina O-Acetiltransferasa/metabolismo , Combinación de Medicamentos , Masculino , Ratas , Ratas Endogámicas , Sustancia Innominada/enzimología , Sustancia Innominada/fisiologíaRESUMEN
The present experiments were undertaken to study whether pharmacological activation of the noradrenergic system would improve age-related deficits in short-term memory. Thus, we investigated the effects the single dose administration (0.1, 0.3, 0.9 and 2.7 mg/kg, subcutaneously) or atipamezole, a specific alpha-2 adrenoceptor antagonist, had on the performance of young and aged rats in a delayed nonmatching to position task. After substantial training, aged rats made more errors at longer delays (4-30 seconds) than did young rats, although the percent correct responses at short delays (0-2 seconds) did not differ between young and aged rats. Atipamezole (0.1-0.9 mg/kg) did not improve the performance of young and aged rats in this task. Moreover, the highest dose (2.7 mg/kg) used increased the number of omissions and increased the latency to collect food pellets, indicating disruption of the performance of rats in this task. According to the present results, alpha-2 antagonist (administered peripherally at a single dose), which increases the release of noradrenaline, did not improve age-related deficit in short-term memory in rats.
Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Envejecimiento/fisiología , Condicionamiento Operante/efectos de los fármacos , Imidazoles/farmacología , Desempeño Psicomotor/efectos de los fármacos , Animales , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
Somatostatin-containing neurons in the hilus of the dentate gyrus are known to be exceptionally vulnerable in experimental models of epilepsy, as well as in human temporal lobe epilepsy. The position of these cells in the circuitry of the dentate gyrus is ideal for gating the activation evoked by afferents from the entorhinal cortex. In the present study we have shown that the loss of hilar somatostatin-containing neurons, and the development of interictal spiking activity induced by sustained perforant pathway stimulation can be prevented by high doses (500 mg/kg), but not by low doses (100 mg/kg) of vigabatrin, an irreversible inhibitor of GABA-transaminase.
Asunto(s)
4-Aminobutirato Transaminasa/antagonistas & inhibidores , Aminocaproatos/farmacología , Hipocampo/efectos de los fármacos , Neuronas/fisiología , Somatostatina/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Hipocampo/fisiología , Masculino , Neuronas/efectos de los fármacos , Ratas , Ratas Endogámicas , VigabatrinRESUMEN
The present study investigated pharmacological consequences of combined cholinergic and serotonergic blockade. Raphe medianus (RM) lesions (5,7-DHT) had no effect on spatial learning, but augmented scopolamine 0.8 mg/kg induced learning deficit. Pilocarpine (4 mg/kg) could reverse scopolamine (0.8 mg/kg), but not scopolamine (0.8 mg/kg) + RM lesion induced spatial learning impairment. However, a higher dose of pilocarpine could restore spatial learning deficit induced by scopolamine (0.8 mg/kg) and RM lesions. These findings support the important role of cholinergic-serotonergic interaction in the regulation of spatial learning and suggests that the combined cholinergic-serotonergic deficit in patient's with Alzheimer's disease may have an impact on therapeutic approaches which seek to normalize AD related cognitive impairments.